RT Journal Article
SR Electronic
T1 Growth Inhibition of Ovarian Tumor–Initiating Cells by Niclosamide
JF Molecular Cancer Therapeutics
JO Mol Cancer Ther
FD American Association for Cancer Research
SP 1703
OP 1712
DO 10.1158/1535-7163.MCT-12-0002
VO 11
IS 8
A1 Yo, Yi-Te
A1 Lin, Ya-Wen
A1 Wang, Yu-Chi
A1 Balch, Curt
A1 Huang, Rui-Lan
A1 Chan, Michael W.Y.
A1 Sytwu, Huey-Kang
A1 Chen, Chi-Kuan
A1 Chang, Cheng-Chang
A1 Nephew, Kenneth P.
A1 Huang, Tim
A1 Yu, Mu-Hsien
A1 Lai, Hung-Cheng
YR 2012
UL http://mct.aacrjournals.org/content/11/8/1703.abstract
AB A recent hypothesis for cancer chemoresistance posits that cytotoxic survival of a subpopulation of tumor progenitors drives the propagation of recurrent disease, underscoring the need for new therapeutics that target such primitive cells. To discover such novel compounds active against drug-resistant ovarian cancer, we identified a subset of chemoresistant ovarian tumor cells fulfilling current definitions of cancer-initiating cells from cell lines and patient tumors using multiple stemness phenotypes, including the expression of stem cell markers, membrane dye efflux, sphere formation, potent tumorigenicity, and serial tumor propagation. We then subjected such stem-like ovarian tumor-initiating cells (OTIC) to high-throughput drug screening using more than 1,200 clinically approved drugs. Of 61 potential compounds preliminarily identified, more stringent assessments showed that the antihelmintic niclosamide selectively targets OTICs in vitro and in vivo. Gene expression arrays following OTIC treatment revealed niclosamide to disrupt multiple metabolic pathways affecting biogenetics, biogenesis, and redox regulation. These studies support niclosamide as a promising therapy for ovarian cancer and warrant further preclinical and clinical evaluation of this safe, clinically proven drug for the management of this devastating gynecologic malignancy. Mol Cancer Ther; 11(8); 1703–12. ©2012 AACR.